Work

Cocaine Upregulates Microglial Lipid Droplet Formation Through Increasing Lipid Synthesis Activity In Vitro and In Vivo

Year: 2026

Type: article

Abstract: A novel subtype of microglia, lipid droplet accumulation microglia (LDAMs), has been identified in the aged brain, which is characterized by sustained inflammation and senescent-like phenotypes. LDAMs are deeply involved in promoting brain aging as well as the pathogenesis of multiple neurodegenerative diseases. Cocaine can alter brain lipidomic profiles, induce microglial activation, and accelerate brain aging. This suggests that cocaine might affect microglial lipid metabolism, which ultimately aggravates aging-related neurological disorders in people with addictions. In this study, we explored the effects of cocaine on microglial lipid metabolism. Our results showed that chronic cocaine administration altered brain lipid profiles and increased LDAM formation in vivo. The increase in LDAMs was accompanied by the upregulation of the senescent marker p53 in the brain. Cocaine also increased lipid droplet (LD) formation in BV2 microglia and primary microglia in vitro. A mechanism study revealed that cocaine increased the levels of SREBP1/2, HMGCR, DGAT1, and FASN, which are critical for lipid synthesis. Overall, our findings demonstrate that cocaine increases LDAM formation in vitro and in vivo. These results indicate that targeting microglia lipid metabolism might be a promising therapeutic approach to mitigate aging-related neurological syndromes in people with cocaine addictions.

Source: Biomolecules

DOI: 10.3390/biom16040526

Authors: Yan Cheng, Brooke Russell, Liam Liyang Guo, Aryan Patel, Yan Y. Sanders, Ming-Lei Guo

Institutions: Eastern Virginia Medical School, Old Dominion University, University of Southern California

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258